Osteoarthritis (OA), the clinical syndrome of joint pain and dysfunction caused by joint degeneration, affects more people than any other joint disease. Osteoarthritis is by far the most common joint disorder in the United States and throughout the world, and is one of the leading causes of disability in the elderly. Knee OA is a common but often difficult problem to manage in primary care. Traditional nonsurgical management, consisting of lifestyle modification, physical therapy and pharmacologic therapy, is often ineffective or leaves residual symptoms. An option for subjects with symptomatic knee OA is a treatment that involves a series of intra-articular injections of hyaluronic acid (hereinafter referred to IA-HA). Sodium hyaluronate is a naturally-occurring constituent of extra cellular matrix, and following intra-articular injection works as a lubricant and shock absorber to relieve pain and improve knee function in OA. Currently, there are 5 IA-HA commercially available products in the United States, SUPARTZ®, SYNVISC®, HYALGAN®, ORTHOVISC® and EUFLEXXA. SYNVISC® was the first IA-HA product launched in the US, and the only aqueous solution of cross-linked derivatives of hyaluronate, others are aqueous solutions of sodium hyaluronate (hereinafter referred to HA-Na). These currently marketed IA-HA products are not apparent differenced in effectiveness. Moreover these products utilize a series of 3 to 5 injections and in other words do not result in longer term responses by a single injection. Therefore new IA-HA product requiring fewer injections would be expected to reduce invasiveness and potential risk of joint infection and result in longer term responses by a single injection.
So far there are many reports about cross-linked hyaluronate with the different cross-linking methods from SYNVISC®, for example cross-linked hyaluronate produced by using multifunctional epoxy compound as a cross-linking group (see Patent Literature 1), photo cross-linked hyaluronate (see Patent Literatures 2 to 4) and intramolecular bridged hyaluronate without a cross linker (see Patent Literature 5). Cross-linked hyaluronate is being investigated as a minimally invasive treatment for pain associated with osteoarthritis of the knee in subjects who have failed to respond adequately to conservative non-pharmacologic therapy and/or simple analgesics, e.g., acetaminophen. For example, it is reported an injected agent for treating joint disorder which was improved to produce a merit of decreasing number of doses by using an agent comprising hyaluronate gel with or without cross-linked structure and phospholipids (see Patent Literature 6).
However, many reports about photo cross-linked hyaluronate product are mainly noted synthesis and general properties of the product and does not carefully examined available and restrictive conditions and properties for an unique application and a specific effect on said cross-linked hyaluronate product. The comparison of antigenicity and irritant property between SYNVISC® and photo cross-linked hyaluronate was reported on Reference (see Non-Patent Literature 1).    Patent Literature 1: JP-B2-5-74571    Patent Literature 2: U.S. Pat. No. 5,462,976    Patent Literature 3: U.S. Pat. No. 5,763,504    Patent Literature 4: U.S. Pat. No. 6,031,017    Patent Literature 5: JP-A-2003-252905    Patent Literature 6: JP-A-2002-348243    Non-Patent Literature 1: “Evaluation of in vivo biocompatibility and biodegradation of photocrosslinked hyaluronate hydrogels” J. Biomed Mater Res. A 70:550-559(2004)